Regulatory aspects of globin synthesis will be studied in intact hemoglobin-synthesizing cells from animals and from patients with a variety of abnormalities related to hemoglobin. A major objective will be to clarify the role of the intracellular pool of free alpha-chains in modifying the rate of synthesis of Beta-chains, and to determine if a mechanism of this kind functions to regulate the coordination of synthesis of the complementary globin chains of hemoglobin. Studies of globin synthesis in vitro by reticulocytes and bone marrow cells of patients with thalassemias and thalassemia-like disorders will also be performed, with the aim of correlating hematologic and globin biosynthetic findings. In conjunction with these studies the development of a simplified procedure for determination of alpha over beta synthesis ratios will be undertaken.